Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000826121 | SCV000967630 | likely pathogenic | Rare genetic deafness | 2018-04-10 | criteria provided, single submitter | clinical testing | The p.Arg351X variant in OTOGL has been identified in a compound heterozygous st ate in 1 individual with hearing loss, who also carried an additional loss-of-fu nction variant in OTOGL (LMM data). It has also been identified in 13/105938 Eur opean chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broa dinstitute.org; dbSNP rs368844341), which is low enough to be consistent with a recessive carrier frequency. This nonsense variant leads to a premature terminat ion codon at position 351, which is predicted to lead to a truncated or absent p rotein. Loss of function of the OTOGL gene is an established disease mechanism i n autosomal recessive hearing loss. In summary, although additional studies are required to fully establish its clinical significance, the p.Arg351X variant is likely pathogenic. ACMG/AMP Criteria applied: PVS1; PM3. |
| Labcorp Genetics |
RCV001382648 | SCV001581527 | pathogenic | not provided | 2023-12-04 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg351*) in the OTOGL gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in OTOGL are known to be pathogenic (PMID: 23122586). This variant is present in population databases (rs368844341, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with OTOGL-related conditions. ClinVar contains an entry for this variant (Variation ID: 667382). For these reasons, this variant has been classified as Pathogenic. |